Recently, not only a maintenance of the effectiveness, safety, and quality of drugs, but also an alleviation of the burden on patients during oral ingestion, has been demanded in the medical sense. This is because there is an increasing trend in the number of patients having a difficulty when taking food (for example, a person with dentures, a person unable to properly chew, or a patient suffering from dysphagia) due to the progressive aging of society, and there is a growing number of patients having a difficulty when taking medicaments by oral administration.
Formulations for oral administration are commonly provided, for example, as solutions, capsules, granules, pills, powders, tablets, or syrups. The definitions of these formulations are described in the Japanese Pharmacopoeia. When a person having a difficulty when swallowing takes such a formulation together with water, a formulation such as powders or granules sometimes exists in the oral cavity, or a formulation such as tablets, pills, or capsules can sometimes cause choking when taken by the person.
To resolve these disadvantages, various pharmaceutical compositions have been proposed. For example, an agent which enables an easy swallowing is known (patent reference 1). According to this agent, a medicament may be formulated with a gel base and a sugar alcohol and, immediately before taking, may be mixed with water or an appropriate liquid substance, to rapidly form a gel (or a jelly) without heating or cooling. According to the disclosures of patent reference 1, when a water-soluble gelatin is used as the gel base, a hard-jelly formulation ideal for an agent which enables an easy swallowing may be obtained, but a gelation time thereof is approximately 45 minutes. Patent reference 1 also discloses that a hard-jelly formulation may be obtained within 1 minute, without heating or cooling, by using a combination of water-soluble gelatin (a gel base) and erythritol (a sugar alcohol). In general, heating or cooling is required to obtain a hard jel by using a gel base. Therefore, it is practically useful to obtain such a hard jel at room temperature in a short time, as disclosed in patent reference 1. However, since sugar alcohols have a high hygroscopicity and are easily liquefied, the combinations thereof with medicaments in which the stability is lost by humidity are limited. Particularly, in the case of the spherical adsorbing carbons described below, an adsorption capacity is decreased while in contact with water, and thus, combinations of the spherical adsorbing carbons and sugar alcohols are inappropriate.
Further, a use of a gel base to enable an easy taking of medicaments, together with a masked agent in which a bad taste (for example, bitterness, astringency, or acidity) of medicaments is alleviated by masking, is known (patent reference 2). Patent reference 2 also discloses that a rapid gelation by only adding water at room temperature without heating or cooling is important, and discloses examples in which a masked bitter antimicrobial agent was used together with a gel base, by using a gelation caused by crosslinking of alginate and a polyvalent metal ion. However, a gelation time of each example was several minutes, and a gelation in a short time was not attained. Further, an agent used together with the gel base was a masked agent which masked bad tastes, and it was not proposed as a general purpose technique.
Furthermore, a use of a gel base for improving difficulty of deglutition of specific antitumor agents is known (patent reference 3). The object of the technique described in patent reference 3 is to provide a jelly formulation capable of enabling an easy taking of a mixing agent of tegafur and uracil as an antitumor agent, for a patient suffering from dysphagia or an intraoral disorder caused as a side effect of the mixing agent. The formulation is provided as a lyophilized product obtained by preparing a jelled gel with a gel base and lyophilizing the jelled gel. Although, when the lyophilized product is returned to a jelled gel formulation by adding water thereto, the jelled gel formulation may be obtained in a short time at room temperature without heating or cooling, it is generally necessary to perform a heating or cooling treatment when preparing the lyophilized product, and it sometimes takes a long time to carry out these treatments. Further, facilities for preparing the lyophilized product are necessary, and that leads to higher costs. Furthermore, in the case of the spherical adsorbing carbons described below, when such a lyophilized product, which is obtained by preparing a jelled gel with a gel base and lyophilizing the jelled gel, is returned to a jelled gel formulation by adding water thereto, when taking, a gel formulation cannot be prepared in a short time because a gas-releasing property of the spherical adsorbing carbons is lost.
An adsorbent for internal use capable of being orally administered and alleviating functional disorders of kidneys or the liver has been developed and is in use (patent reference 4). The adsorbent for internal use consists of a porous carbonaceous substance having specific functional groups (i.e., a modified spherical activated carbon); is very safe and stable to a body; and has a useful selective adsorbability, that is, an excellent adsorbability of harmful substances in the presence of a bile acid in the intestine, and a low adsorbability of useful substances such as digestive enzymes in the intestine. Further, the adsorbent for internal use is widely and clinically used for a patient suffering from a disorder of a liver or renal function, as an oral medicament having few side effects such as constipation. The adsorbent disclosed in patent reference 4 is manufactured by preparing spherical activated carbons from pitches such as petroleum pitch as a carbon source, and subjecting the spherical activated carbons to an oxidation treatment and a reduction treatment. Further, an adsorbent for oral administration in which the above selective adsorbability (i.e., an excellent adsorbability of harmful substances and a low adsorbability of useful substances in the intestine) is improved is known (patent reference 5). The adsorbent for oral administration disclosed in patent reference 5 is based on the findings that the selective adsorbability is improved when a volume of pores having a pore diameter of 20 to 15000 nm is 0.04 mL/g or more and less than 0.10 mL/g, and thus, can effectively adsorb harmful substances, and is extremely useful for diseases in which a suppression of the adsorbability of useful substances in the intestine is desired.
The adsorbent for internal use is generally provided in the form of fine granules or capsules. Since a dose is relatively large, it was desirable to improve the ease of taking. For example, when taking fine granules, some patients dislike a feeling of any residual in the oral cavity. Further, many patients feel repulsion and pain when taking relatively large medicaments such as capsules, and further, many patients cannot take granules or capsules without taking in a large quantity of water.
Further, for patients suffering from a renal disease or renal failure, an amount of water to take is limited, and such patients are required to take minimal water when ingesting granules or capsules. Therefore, patients who essentially need a large quantity of water when taking granules or capsules feel intense pain when doing so.
[Patent Reference 1] Japanese Unexamined Patent Publication (Kokai) No. 2002-104997
[Patent Reference 2] Japanese Unexamined Patent Publication (Kokai) No. 2000-103730
[Patent Reference 3] Japanese Unexamined Patent Publication (Kokai) No. 11-322606
[Patent Reference 4] Japanese Examined Patent Publication (Kokoku) No. 62-11611
[Patent Reference 5] Japanese Patent No. 3522708